Supplementation of the aryl hydrocarbon receptor ligand indole-3-carbinol protects mice from Clostridium difficult associated disease. (MUC5P.762)

Abstract

Abstract We have previously presented the dramatic benefit in survival that the dietary aryl hydrocarbon receptor (AHR) ligand indole-3-carbinol (I3C) confers in C. difficile disease in mice. Other groups have demonstrated that γδ T cells and Tregs play an important role in preventing other models of colitis. The current study sought to determine whether dietary I3C could protect mice from C. difficile by increasing the amounts of protective γδ T cells and Tregs. Furthermore, we examined the role of I3C in preventing antibiotic mediated dysbiosis. Mice were fed an experimental AHR ligand free diet (“base”) or the same diet supplemented with I3C and then infected with C. difficile. Pre-infection, base mice had less γδ T cells and Tregs in their cecum compared to I3C mice. Furthermore, I3C mice had a more robust and less pathologic microbiome pre-infection. Post-infection, I3C mice continued to have higher levels of γδ T cells and Tregs. These data suggest that AHR ligand supplementation can protect the host from C. difficile by reducing antibiotic associated dysbiosis as well as augmenting the local immune system to be more protective from C. difficile associated inflammation. Given the poor treatment options currently available as well as the high morbidity of infection, this represents an exciting new therapeutic possibility.